There is an urgent need for new approaches for the detection and treatment of pancreatic cancer. The overall hypothesis of this research is that immune biomarkers may be useful for the early detection of disease and guide approaches for immune therapy in the treatment of pancreatic cancer. This group focuses on the major ligand for natural killer (NK) cells – MHC class I-related chain protein (MICA). The binding of MICA to NK cells promotes the elimination of tumor cells by NK cells. However, tumors release MICA into circulation and thus escape from NK cell immune surveillance. Several previous studies examined s-MICA-pancreatic cancer association but they were lacking information on covariates that may confound and modify this association. Specifically, it is necessary to assess functional MICA gene variants.
The objective of this project is to define the association between s-MICA and pancreatic cancer using a study design that appropriately assesses the confounding and modifying effects of environmental factors and genetic polymorphisms. The main hypothesis is that the functional variants in the MICA gene play a role in the risk of pancreatic cancer development and modulate s-MICA-pancreatic cancer association. To test this hypothesis, these researchers will assess s-MICA plasma levels across demographic and lifestyle characteristics and determine the association of polymorphisms in MICA genes with s-MICA levels and pancreatic cancer risk. Finally, they will identify whether s-MICA and pancreatic cancer-association is modulated by environmental and genetic characteristics. Given the MICA role in NK cell tumor surveillance, understanding the s-MICA accumulation in the blood is clinically important because the inhibition of the accumulation will provide a novel opportunity to control pancreatic tumor progression. Also, genetic studies of MICA are essential, because alleles expressed by individual patients will affect s-MICA levels in different ways and, thus, likely require tailored therapies.